PS30: Pivotal Trial Designs for New and Next Generation Cell and Gene Therapies

The past decade has seen significant advancements for cell and gene therapies (CGTs). With the promising treatment effect brought by the currently approved CGTs, there are noticeable limitations, such as manufacturing delays and durability of response, motivating continued development in this field. The next-generation CGTs, such as allogeneic and other products, can potentially benefit patients by either addressing the limitations of currently available therapies without compromising efficacy or by further enhancing efficacy. However, the development of new CGTs faces unique challenges as highly efficacious approved first-generation products could be potentially established as the current standard of care (SOC). When the approved CGT products are recommended as the comparator, questions arise, especially, is it feasible to set up a head-to-head comparison between the new and the approved CGT products? What could be the feasible study design options to evaluate the effectiveness of new CGT products? This session will examine the challenges of developing new CGTs using conventional randomized control and single arm trials, as well as introduce innovative design strategies for pivotal trials. Given recent regulatory publications, this topic is particularly timely and essential for bringing new products to patients. Notably, a manuscript by the American Statistical Association Cell and Gene Therapy Scientific Working Group to address these challenges has been published (Anderson, Xu, Degtyarev et al. J Biopharm Stat 2026). The proposed session will feature transdisciplinary speakers and panelists from academia, regulatory agencies, and industry. One speaker will provide perspective from the clinical point of view for new products when highly effective therapies are already approved. Another speaker will provide an industry perspective and outline potential trial design options. CAR T-cell products may be used as primary examples. For the last part of the session, invited panelists from industry and FDA will provide commentary on relevant discussion questions. On behalf of the American Statistical Association Cell and Gene Therapy Scientific Working Group, we believe that this session will foster a constructive dialogue among stakeholders to address these unique development challenges.